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The aim of the present study was to assess the role of endothelin (ET) in ischemia-reperfusion (I/R)-induced mucosal injury. Mucosal permeability ([sup.51]Cr-EDTA clearance) and tissue myeloperoxidase (MPO) activity were significantly increased after 30 rain of ischemia followed by 30 min of reperfusion. The I/R-induced increases in mucosal permeability and polymorphonuclear leukocyte (PMN) infiltration were significantly attenuated by pretreatments with E[T.sub.A] (BQ-485) and/or E[T.sub.B] (BQ-788) receptor antagonists. Monoclonal antibody (MAb) directed against intercellular adhesion molecule-1 (ICAM-1; MAb 1A29) and superoxide dismutase (SOD) pretreatments significantly attenuated the increased mucosal permeability and PMN infiltration in a similar manner as with ET receptor antagonists. Superior mesenteric artery blood flow was significantly reduced during the reperfusion period. Both ET receptor antagonists caused a significant rise in blood flow compared with an untreated I/R group. In conclusion, our data suggest that E[T.sub.A] and/or E[T.sub.B] receptors, ICAM-1, and superoxide play an important role in I/R-induced mucosal dysfunction and PMN infiltration. Furthermore, ET is involved in the pathogenesis of postreperfusion-induced damage and beneficial effects of ET receptor antagonism are related to an improvement of disturbed blood flow during the reperfusion period. mucosal permeability; mucosal injury; BQ-485; BQ-788; superoxide dismutase

Byline: I.F. Tugtekin (1), P. Radermacher (1), M. Theisen (1), M. Matejovic (2), A. Stehr (3), F. Ploner (4), K. Matura (5), C. Ince (5), M. Georgieff (1), K. Trager (1) Keywords: Endotoxin Ileal-mucosal-arterial PCO2 gap Orthogonal polarization spectral imaging Lactate/pyruvate ratios Remission spectrophotometry Villus microcirculation Abstract: Objective: To investigate whether an increased ileal-mucosal-arterial PCO.sub.2 gap (IPCO.sub.2) during hyperdynamic porcine endotoxemia is associated with impaired villus microcirculation. Design: Prospective, randomized, controlled, experimental study. Setting: Animal research laboratory. Animals: Twenty-two domestic pigs. Interventions: After baseline measurements, anesthetized and ventilated pigs received continuous i.v. endotoxin (ETX, n=12) for 24 h or placebo (SHAM, n=10). Measurements and results: Before, as well as 12 and 24 h after, the start of endotoxin or saline portal venous blood flow (Q.sub.PV, ultrasound flow probe) and lactate/pyruvate ratios (L/P), the ileal-mucosal-arterial IPCO.sub.2 (fiberoptic sensor) and bowel-wall capillary hemoglobin O.sub.2 saturation (%Hb-O.sub.2-cap, remission spectrophotometry) were assessed together with intravital video records of the ileal-mucosal microcirculation (number of perfused/heterogeneously perfused/unperfused villi) using orthogonal polarization spectral imaging (CYTOSCAN A/R) via an ileostomy. At 12 and 24 h endotoxin infusion, about half of the evaluated villi were heterogeneously or unperfused which was paralleled by a progressive significant increase of the ileal-mucosal-arterial IPCO.sub.2 and portal venous L/P ratios, whereas Q.sub.PV as well as both the mean %Hb-O.sub.2-cap and the %Hb-O.sub.2-cap frequency distributions remained unchanged. By contrast, in the SHAM-group, mucosal microcirculation was well-preserved, and none of the other parameters were influenced. Conclusions: We conclude that an increased ileal-mucosal-arterial IPCO.sub.2 during porcine endotoxemia is related to impaired villus microcirculation. A putative contribution of disturbed cellular oxygen utilization resulting from 'cytopathic hypoxia' may also assume importance. Author Affiliation: (1) Sektion Anasthesiologische Pathophysiologie und Verfahrensentwicklung, Universitatsklinik fur Anasthesiologie, Parkstrasse 11, 89075, Ulm, Germany (2) I. Interni Kliniky, Karlova Universita, Plzen, Czech Republic (3) Klinik und Poliklinik fur Chirurgie, Universitatsklinikum, Regensburg, Germany (4) Abteilung Anasthesiologie und Reanimation, Bezirkskrankenhaus, Sterzing, Italy (5) Afdeling Experimentele Anaesthesiologie, Academisch Medisch Centrum, Amsterdam, The Netherlands Article History: Received Date: 26/07/2000 Accepted Date: 29/12/2000 Article note: Final revision received: 7 December 2000 Electronic Publication

The role of microvascular perfusion deficits in mucosal injury in septic rats has been investigated. The goal was to determine whether mucosal injury in the small intestine takes place in a normotensive model of sepsis and whether such injury is linked to microvascular perfusion deficits. Results show that injury to the mucosa of the small intestine in septic rats was not associated with concurrent microvascular perfusion deficits.

Mast cells regulate the gastric-mucosal integrity by releasing mediators such as IL-1 and nitric oxide. The increase in the number of mast cells does not increase mucosal susceptibility to injury induced by a topical irritant. But, the activation of mast cells with antigen causes gastric changes due to the activation of the irritant, which is mediated by a peptidoleukotriene-dependent mechanism.

Intestinal permeability is examined by extensively employing the calculations of plasma clearance of water-soluble molecules. Various experimental states show the employment of blood-to-human clearance of 51-chromium (Cr) labeled EDTA, a hydrophilic molecule with low molecular weight and small molecular radius. The transfer of these small molecules is not hindered by the vascular wall. The intestinal interstitium shows quick equlibration of 51Cr-EDTA, which inhibits the transfer of the marker from blood to lumen by the epithelial cell layer of the mucosa.